Discussion of interesting or befuddling cases related to pulmonary and critical care medicine.

Monday, February 20, 2006

IPF?

A patient with shortness of breath. An open lung biopsy in 2002 was consistent with UIP:

Interstitial fibrosis predominantly distributed peripheral subpleural areas of the bx. Also multiple foci of active fibrosis. Also foci of reactive pneumocytes and expansion of some of the airspaces with incipient honeycomb formation. Occasional foci of mild non-specific chronic inflammation and also foci of alveolar cells/macrophages within airspaces. Areas of normal lung parenchyma interspersed within the fibrotic foci. No granulomas. Grocott stain negative. The overall histologic picture is in keeping with usual interstitial pneumonia (UIP).

But here are the CT's:1999: "Multiple patchy opacities in the right upper lobe with one more nodular appearing opacity seen on images 16-18 are of uncertain etiology. Scattered unenlarged lymphadenopathy and one single borderline enlarged subcarinal node is seen. Inflammatory ( BOOP, MAI, etc. ) cause is more likely but malignant etiology should be excluded.

2002: Thickening of the interlobular septa and honeycombing peripheral and basilar distribution. In addition, bronchiectasis is present in the lower lobes and ground glass appearance persists, more predominant in the lower lobes.

So we have a biopsy with "UIP" (RML and RLL open lung, done after the above HRCT and after a nondiagnostic bronchoscopy). Is anyone bothered by the previous CT's suggesting an inflammatory look to it (i.e. ground glass)? In my opinion this is a previous inflammatory process (perhaps NSIP, BOOP, HP, etc) that has progressed to fibrosis; do you feel that the biopsy showing foci of fibroblasts represent true idiopathic IPF?

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When was the biopsy done? It's possible that they are true-true and unrelated-i.e. in 1999 there was an inflammatory process that resolved, and she went on to develop IPF over the ensuing years.

The distribution on CT scan--peripheral and basilar--would be more typical of UIP than HP. The CT mentions ground glass opacities; these would not be typical, if they are a prominent feature. So how extensive were they.

Fibroblastic foci are mentioned, and this is consistent with UIP (although they can be seen in other ILD's, they should not be a prominent feature). The "reactive pneumocytes" and "mild inflammatory" infiltration, with a lack of granulomas also point toward UIP.

Although honeycombing is noted on the CT, there is no comment of honeycombing on the biopsy.

So, this all sounds like UIP, but we know from recent studies that there can be significant variability in what a pathologist reads as UIP, depending on their experience and the setting. So, bottom line: if the clinical progression, radiographic appearance, and pathology are consistent with UIP, than that is the most likely diagnosis.

But if we assume the ground glass and other findings on previous CT's going back to 1999 represent the patient's current disease, does the biopsy "trump" these CT findings (atypical to say the least for UIP)? In our curren understanding, the UIP dx on biopsy supersedes everything, even when an alternative is more rationle (uring fellowship for example, typical UIP pattern on a biopsy led to dx of idiopathic IPF/UIP even though that patient was a pigeon breeder for 30 years).So in sum, does the presence of ground glass on ct's a few years before have any bearing on the UIP dx made on subsequent biopsy?

UIP is the histologic correlate of IPF. 30 years of HP can lead to end-stage lung that looks like UIP, and if you put several expert pathologists in the same room, there will be disagreement about whether to call that chronic HP (based on history), UIP, or "end-stage lung."

In the case you presented, the problem is that we don't know if the ground glass seen in 1999 has any relationship to the current findings. We also don't know if ground-glass patterns would be more common if we look 8 years earlier in patients who went on to develop IPF.

I think that the ground glass opacities in 1999 have to be looked at in context of the disease pattern now. Unfortunately, it really may not matter at this point whether this is IPF, HP, NSIP, or any other IP, as prognosis is driven by the presence of honeycombing, and you would probably treat them all the same. There is no further diagnostic study that can be done. So, in the absence of a compelling evidence for an alternative diagnosis, if you think the pathologist is reliable and accurate, I think the diagnosis is probably IPF.

Of course, you could always have the biopsies sent elsewhere for another opinion.

In terms of prognosis, UIP found on a biopsy trumps everything regardles of the etiology. 30 years of HP, as it turns out, is hazardous to your health, just as much as is "IPF".

IPF however, implies that the fibrosis is not secondary to any know lung injury, or autoimmune disease. Hard to know whether this patients condition qualifies as IPF or not. But she is short of breath, and with this biopsy, her prognosis is likely very poor.

JH brings up a good point regarding the utter lack of inter-reader agreement, even amongst experienced pulmonary pathologists. It's be good to get a seconf pathologist to review this, especially with tha accompanying history (was your pathologist privvy to the history you provided us when he/she read the slides for example?)

I agree that getting a second opinion is a good idea. There certainly seems to be interobserver variability in making this diagnosis.

Let me relate a story of a recent patient of mine. He presented with a CT showing RUL and LLL and some RLL dense airspace consolidation and hypoxemia (50% FiO2). He went to open Lung biopsy. Diagnosis: UIPhe was treated with prednisone and imuran and 7 months later he is now off oxyegen.So was this UIP.? Well the path was reviewed by a second pathologist who agreed with the UIP diagnosis.

But there is no way this was UIP given his response to therapy.

When an open lung biopsy is obtained you are grabbing tissue from the lung periphery and I suspect if the patient has co-existing UIP with another disease - you may only see the UIP.

I think the path and radiology have to correllate to make the diagnosis. The path does not trump clinical history and radiology IMHO.

By the way , this is also the best argument on why we should "treat" our UIP patients with a 3 to 6 month course of prednisone and imuran..not to treat UIP but to definatively rule out other treatable diagnosis.